|
|
Background Young, trained athletes may have abnormal 12-lead electrocardiograms (ECGs) without evidence of structural cardiac disease. Whether such ECG patterns represent the initial expression of underlying cardiac disease with potential long-term adverse consequences remains unresolved. We assessed long-term clinical outcomes in athletes with ECGs characterized by marked repolarization abnormalities.
Methods From a database of 12,550 trained athletes, we identified 81 with diffusely distributed and deeply inverted T waves (
Results Of the 81 athletes with abnormal ECGs, 5 (6%) ultimately proved to have cardiomyopathies, including one who died suddenly at the age of 24 years from clinically undetected arrhythmogenic right ventricular cardiomyopathy. Of the 80 surviving athletes, clinical and phenotypic features of hypertrophic cardiomyopathy developed in 3 after 12±5 years (at the ages of 27, 32, and 50 years), including 1 who had an aborted cardiac arrest. The fifth athlete demonstrated dilated cardiomyopathy after 9 years of follow-up. In contrast, none of the 229 athletes with normal ECGs had a cardiac event or received a diagnosis of cardiomyopathy 9±3 years after initial evaluation (P=0.001).
Conclusions Markedly abnormal ECGs in young and apparently healthy athletes may represent the initial expression of underlying cardiomyopathies that may not be evident until many years later and that may ultimately be associated with adverse outcomes. Athletes with such ECG patterns merit continued clinical surveillance.
2 mm in at least three leads) who had no apparent cardiac disease and who had undergone serial clinical, ECG, and echocardiographic studies for a mean (±SD) of 9±7 years (range, 1 to 27). Comparisons were made with 229 matched control athletes with normal ECGs from the same database.
Despite several observational and cross-sectional surveys performed over the past 30 years exhaustively describing ECG findings in trained athletes,1,2,3,4,5,7,8,9,10,11,12,14 the long-term clinical significance of such abnormal patterns has remained largely unresolved. Therefore, in the present longitudinal study, we evaluated the clinical outcomes associated with markedly abnormal ECGs characterized by distinctive repolarization patterns in young, trained athletes.
Methods
Since 1982, the Italian government has required by law that all citizens participating in officially sanctioned competitive sports undergo preparticipation screening to rule out the presence of cardiovascular disease that could be associated with increased risk during training and competition.18 At the Institute of Sports Medicine and Science, young competitive athletes selected for inclusion on national teams undergo a medical evaluation that routinely includes a medical history, a physical examination, 12-lead and exercise ECGs, and a two-dimensional echocardiogram. In addition, athletes are selectively referred to this institution from satellite sports medical centers when ECG abnormalities or abnormal findings from their medical history or physical examination are detected. All the records of clinical data on these athletes are kept in a database maintained by the institute.
At the time each subject is enrolled in the database, a standard 12-lead ECG is obtained with the subject in the supine position during quiet respiration and recorded at 25 mm per second. The ECG tracing is obtained just before the echocardiographic examination and more than 24 hours after the last athletic activity. Incremental exercise testing until exhaustion is performed on a bicycle ergometer (Cardioline SDS 3D or Cardioline ETC system).
Echocardiographic studies are performed with commercially available instruments (Sonos 5500, Philips). The extent and distribution of left ventricular hypertrophy are assessed from two-dimensional echocardiography, as previously described.19 Echocardiographic studies routinely include a search for the normal position of the ostia and the proximal course of the epicardial coronary arteries.20
Study Design
We conducted a matched case–control study to compare the long-term outcomes in athletes who had marked repolarization abnormalities with the outcomes in a similar group of athletes who had normal ECGs. The study design was approved by the review board of the institute. Written informed consent was waived for the elite athletes examined in our institute within the medical program for the Italian Olympic team (57 of the study group and all 229 of the control group), because these athletes were undergoing a standard clinical evaluation pursuant to Italian law and institute policy. Written informed consent for this investigation was obtained from the remaining 24 athletes, who were referred to the institute for evaluation of specific clinical findings. The analysis was funded by the Italian National Olympic Committee.
We reviewed ECG data from the database for all athletes evaluated at the institute between 1979 and 2001. We identified those subjects in the database with ECGs showing marked repolarization abnormalities, defined as inverted T waves (2 mm in depth) in at least three leads (exclusive of standard lead III), and predominantly in the anterior and lateral precordial leads V2 through V6 (Figure 1A, 1B, and 1C).
|
A control group of athletes with normal ECGs and no evidence of structural cardiac disease was assembled from athletes examined at the Institute of Sports Medicine and Science between 1980 and 2000. From this cohort, we initially selected every 20th consecutive athlete (according to the date of enrollment in the database) with a normal ECG pattern. From this group, we selected a subgroup of athletes that was similar to the study group with respect to age, sex, and duration of follow-up (Figure 2).
|
Data are expressed as means ±SD. Differences between means were assessed by a paired or unpaired Student's t-test, as appropriate. Differences between proportions were assessed with the chi-square test. The rates of development of cardiac disease in subjects with repolarization abnormalities and controls were compared with the use of Fisher's exact test or the chi-square test, as appropriate. A two-tailed P value of less than 0.05 was considered to indicate statistical significance. Logistic-regression analysis was used to analyze the effect of several variables (duration of follow-up, age at the time of change in the ECG, left-ventricular-mass index, and body-surface area) on changes in ECG patterns during the follow-up period. The product-limit method of survival analysis was performed to assess the time to change in the ECG pattern.26
Results
Study and Control Cohorts
Between 1979 and 2001, a total of 12,880 athletes were examined in our institute, of whom 12,550 had ECG and echocardiographic data sufficient for inclusion in this study (Figure 2). From this database, we identified 123 subjects (1%) who presented with marked repolarization abnormalities. Of these 123 athletes, 39 had echocardiographic and clinical evidence of structural heart disease on initial evaluation, including most commonly hypertrophic cardiomyopathy (17 subjects) but also mitral-valve prolapse (6 subjects), arrhythmogenic right ventricular cardiomyopathy (4), systemic hypertension (4), dilated cardiomyopathy (3), aortic stenosis with bicuspid valve (3), ischemic heart disease (1), and myocarditis (1); these 39 athletes were therefore excluded from further analysis.
The remaining 84 athletes showed no evidence of structural cardiovascular disease at initial evaluation according to echocardiographic study or other selected diagnostic tests performed as appropriate (e.g., myocardial scintigraphy, cardiac magnetic resonance imaging, and coronary arteriography). Of these 84 athletes, 81 had at least two clinical evaluations (with 12-lead ECG and echocardiogram), and therefore they constituted the final study group. The control group included 229 athletes similar in age, sex, and duration of follow-up to the study group (Figure 2).
In 54 of the 81 athletes (67%), other ECG abnormalities were associated with the deeply inverted T waves, including increased R- or S-wave precordial lead voltages (Sokoloff–Lyon index 30 mm) in 42, deep and narrow Q waves (2 mm) in 8, left atrial enlargement in 6, diminished R wave in the anterior precordial leads in 5, and left-axis deviation (–30 degrees) in 2. The QT intervals were normal in each of these athletes, and none had evidence of the Brugada syndrome.27
Demographic Characteristics
The 81 subjects in the study group included 63 males and 18 females who were 23±6 years of age (range, 15 to 38) at the initial evaluation and 32±10 years (range, 17 to 63) at the most recent assessment (Table 1). The athletes were engaged in a variety of sporting disciplines, most commonly soccer (17 subjects), rowing or canoeing (16), track and field (7), swimming (5), and cycling (4). All had participated in regular training and competition for a substantial number of years (mean, 12; range, 3 to 26), and 57 (70%) had achieved recognition at national or international events, including 14 who had participated in the Olympic Games.
|
Changes during Follow-up
Follow-up data were available for a mean of 9±7 years (range, 1 to 27) in the group with marked repolarization abnormalities and for a mean of 9±3 years (range, 3 to 19) in the control group. At the most recent evaluation, 63 of the 81 athletes with an abnormal repolarization pattern (78%) were still engaged in regular training and competition, whereas 17 (21%) had discontinued training and competition and 1 had died.
During the follow-up period, repolarization abnormalities on the 12-lead ECG remained essentially unchanged (or showed deeper T-wave inversion) in 54 athletes (67%). In the remaining 27 athletes, ECG patterns either normalized completely (in 12) or became less abnormal (in 15) by showing reduced T-wave inversion (maximum T-wave inversion from 4.5±4 to 2.9±2 mm, P<0.001), with fewer leads involved (from 6.1±1 to 4.5±3 mm, P<0.001) (Figure 3A and 3B). The mean period for abnormal ECG patterns to revert (i.e., either normalize or improve) was 11.4±3.5 years (median, 8.5). Logistic-regression analysis showed that normalization or improvement in ECG repolarization patterns during the observation period was associated with the length of the follow-up (P<0.001).
|
Clinical Outcome
Of the 81 athletes with abnormal ECGs, evidence of cardiomyopathy developed in 5 (6%) during the period of follow-up and evidence of other cardiovascular disorders developed in 6 (7%), for a total of 11 subjects (14%) (Table 1 and Table 2). One participant died suddenly at the age of 24 years (1 year after initial evaluation) from clinically undetected arrhythmogenic right ventricular cardiomyopathy (Figure 4). Of the 80 surviving athletes, clinical and phenotypic features of hypertrophic cardiomyopathy developed, during an average follow-up period of 12±5 years, in 3 subjects at the ages of 27, 32, and 50 years, including 1 who had an aborted cardiac arrest (after 16 years of follow-up). These athletes showed relatively mild left ventricular hypertrophy (wall thickness, 13 to 16 mm) in association with a nondilated cavity (end-diastolic dimension, 47 to 50 mm) in the absence of systemic hypertension, as well as mild systolic anterior motion of the mitral valve in one and ventricular fibrillation or ventricular tachycardia in two.21 Dilated cardiomyopathy (left ventricular end-diastolic dimension, 62 mm; ejection fraction, 40%) developed in another athlete during a 9-year follow-up.22 Detailed descriptions of the clinical course in these five patients are available in the Supplementary Appendix, available with the full text of this article at www.nejm.org.
|
|
In contrast, none of the 229 athletes with normal ECGs, representing the control group, had evidence of cardiomyopathy at follow-up (P=0.001 for the comparison with the rate of cardiomyopathy in those with abnormal ECGs) (Table 1). Only four (2%) had evidence of other cardiovascular disorders (Table 1 and Table 2). In one of these athletes, myocarditis developed at the age of 19 years, 1 year after the initial evaluation; in another, pericarditis developed at the age of 28 years, 2 years after the initial evaluation. In addition, supraventricular tachycardia was identified in two athletes after 2 and 3 years of follow-up (requiring radiofrequency ablation in one). The overall incidence of cardiovascular abnormalities was therefore 14% (11 of 81 athletes) in the study group, as compared with 2% (4 of 229 athletes) in the control group (P=0.001).
In our study population, the negative predictive value of a normal ECG was 100% to exclude the development of cardiomyopathy and 98% to exclude the development of any cardiac abnormality. The positive predictive value of an abnormal ECG was 6% for cardiomyopathy and 14% for any cardiac condition. Among the study participants in whom cardiomyopathy subsequently developed, none showed improvement or resolution of their marked repolarization abnormalities in the resting ECG over time (Table 2).
Discussion
Highly trained athletes occasionally present with abnormal ECG patterns, many of which are often regarded as innocent expressions of the cardiac remodeling associated with systematic and intensive exercise conditioning.1,2,3,4,5,6,7,8,9,10,11,12,13 However, in a small but important subgroup of athletes,14 ECGs may be markedly abnormal and even bizarre in appearance, suggesting the presence of a pathologic cardiac condition such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy.21,28,29 Abnormal repolarization patterns have previously been reported to occur in 2 to 4% of large populations of trained athletes who are young adults (aged 18 to 35 years).14,30
Such distinctly abnormal ECGs pose a diagnostic question when they occur in the absence of detectable structural heart disease. These ECG findings may represent the initial, subtle expression of cardiac disease with adverse long-term clinical consequences.15,16,17 Alternatively, these ECGs may be innocent expressions of the cardiac remodeling associated with "athlete's heart."14 In an effort to clarify this important issue, we undertook the present long-term study to investigate the clinical outcomes of a unique subgroup of elite competitive athletes who initially presented with marked repolarization abnormalities on the ECG in the apparent absence of cardiac disease.
In the present analysis, we found distinctly abnormal repolarization patterns in 1% of our large population of athletes. A subsequent diagnosis of cardiomyopathy was made in 5 (6%) of the 81 athletes with such abnormalities who had no previous evidence of cardiac disease. Furthermore, two of these five athletes had major adverse cardiac events (a rate of 0.3% per year). One survived a cardiac arrest due to hypertrophic cardiomyopathy and one died suddenly of arrhythmogenic right ventricular cardiomyopathy; both were without previous cardiac symptoms.
In contrast, neither cardiomyopathy nor a major adverse cardiac event subsequently developed in any of the patients in the control group. Other cardiovascular disorders occurred in the study group (systemic hypertension, coronary artery disease, myocarditis, and supraventricular tachycardia) and the control group (myocarditis, pericarditis, and supraventricular tachycardia), although it is not likely that these conditions were related to the original abnormal ECGs.
Our experience, therefore, provides a useful perspective on isolated, markedly abnormal ECGs in young, asymptomatic athletes. Contrary to previous reports describing such ECG patterns as innocent manifestations of "athlete's heart" without adverse clinical consequences,14,31 the present study shows that these abnormal ECGs may represent the initial expression of genetic cardiac disease, preceding by many years phenotypic expression and adverse clinical outcomes.32
Another insight derived from our investigation is the potential difficulty in clinical recognition of both arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy, particularly in young, physically active (and asymptomatic) people. Arrhythmogenic right ventricular cardiomyopathy was not identified during the lifetime of our athlete who died suddenly, despite the heightened awareness of that disease within the Italian national preparticipation screening program.18 In retrospect, the clinical evaluation did not create a strong suspicion of this diagnosis in this athlete because the repolarization abnormalities were not those most typically identified in this disease (T-wave inversion was diffuse rather than confined to the anterior precordial leads). Furthermore, echocardiography did not show marked enlargement of the right ventricular chamber or segmental wall-motion abnormalities, and electrophysiological study with programmed ventricular stimulation did not induce ventricular tachyarrhythmia (see the Supplementary Appendix).
On the basis of our data, it seems reasonable that, in the setting of large-scale preparticipation screening, ECGs showing marked repolarization abnormalities may be useful for identifying athletes at risk for the subsequent development of structural heart disease. These observations underscore the importance of greater diagnostic scrutiny and continued clinical surveillance of trained athletes who present with such distinctly abnormal ECGs. On the basis of our observations, it seems likely that serial ECG alone is not sufficient for such surveillance, but echocardiography and selective additional testing are necessary to clarify the cardiac diagnosis. Conversely, the finding of a normal ECG during preparticipation screening can be regarded as reasonably reliable evidence to exclude the presence of potentially lethal cardiac disease and can serve as a source of reassurance to young athletes.33
In summary, we investigated the clinical course of trained athletes with marked repolarization abnormalities on the ECG. Such abnormalities were uncommon but were associated with a disproportionately increased risk of the subsequent development of structural cardiac disease.
Supported by the Italian National Olympic Committee.
No potential conflict of interest relevant to this article was reported.
Source Information
From the Institute of Sports Medicine and Science, Italian National Olympic Committee, Rome (A.P., F.M.D.P., F.M.Q., R.D.L., A.S., A.B.); the Institute of Pathology, University of Padua Medical School, Padua (C.B., G.T.); the Department of Experimental Medicine, University La Sapienza, Rome (F.C.); and the Department of Diagnostic and Laboratory Services and Forensic Medicine, University of Modena and Reggio Emilia, Modena (G.P.) — all in Italy; and the Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis (B.J.M.).
Address reprint requests to Dr. Pelliccia at the Institute of Sports Medicine and Science, Via dei Campi Sportivi 46, 00197 Rome, Italy, or at ant.pelliccia{at}libero.it.
References
| |||||||||||||||||||||||||||||||||||||||||||||||||
Related Letters:
Athletes with Repolarization Abnormalities
Efthimiadis G. K., Meditskou S., Parcharidis G. E., Galvin J. M., Arnold J. R., Karamitsos T. D., Petersen S. E., Pelliccia A., Maron B. J.
Extract |
Full Text |
PDF
N Engl J Med 2008;
358:2296-2298, May 22, 2008.
Correspondence
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | TERMS OF USE | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2009 Massachusetts Medical Society. All rights reserved. |
Previous
